TCRD and Pharos 2021: mining the human proteome for disease biology.
paper
Cited
Public
- Authors
- Sheils, Timothy K; Mathias, Stephen L; Kelleher, Keith J; Siramshetty, Vishal B; Nguyen, Dac-Trung; Bologa, Cristian G; Jensen, Lars Juhl; VidoviΔ, DuΕ‘ica; Koleti, Amar; SchΓΌrer, Stephan C; Waller, Anna; Yang, Jeremy J; Holmes, Jayme; Bocci, Giovanni; Southall, Noel; Dharkar, Poorva; MathΓ©, Ewy; Simeonov, Anton; Oprea, Tudor I
- Year
- 2021
- Journal
- Nucleic acids research
- PMID
- 33156327
- DOI
- 10.1093/nar/gkaa993
- PMCID
- PMC7778974
In 2014, the National Institutes of Health (NIH) initiated the Illuminating the Druggable Genome (IDG) program to identify and improve our understanding of poorly characterized proteins that can potentially be modulated using small molecules or biologics. Two resources produced from these efforts are: The Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/) and Pharos (https://pharos.nih.gov/), a web interface to browse the TCRD. The ultimate goal of these resources is to highlight and facilitate research into currently understudied proteins, by aggregating a multitude of data sources, and ranking targets based on the amount of data available, and presenting data in machine learning ready format. Since the 2017 release, both TCRD and Pharos have produced two major releases, which have incorporated or expanded an additional 25 data sources. Recently incorporated data types include human and viral-human protein-protein interactions, protein-disease and protein-phenotype associations, and drug-induced gene signatures, among others. These aggregated data have enabled us to generate new visualizations and content sections in Pharos, in order to empower users to find new areas of study in the druggable genome.
Chart of the TDL changes between TCRD v3.0 and v6.7. The decrease of Tdark and subsequent increase of other development levels shows an overall increase in target illumination.
List of targets associated with asthma, filtered by Data Source: Expression Atlas, and filtered by Expression Atlas log2foldchange value (A). Also shown is the Disease Association Details column, with additional association-specific details (B).
Browse targets page, showing new numeric slider facets for Log PubMed Score range (A), searchable protein Family filter panel (B) and improved target card view (C). The Log PubMed Score filter also shows the definition section displayed.
Target details view for ACE2, showing the new table of contents section (A), Target overview section (B) and TDL section (C).
IDG generated resources for ACE2, consisting of small molecule reagents (A), and data (B). Targets with mouse cell lines, such as GPR68, also have information about that resource (C) as well as a mouse tissue expression viewer (D). Other data can include, such as the case for CACNA2D4, mouse phenotype (E) and cell line (F) data. Supplementary Table S2 contains a full breakdown of data types and fields collected.
Target details view for ACE2, showing the improved Protein Data Bank data viewer (A) and predicted viral interactions (B).
Target details view for ACE2, showing the tissue expression section, with highlighted tissues (A), and protein to protein interaction section (B). The frequency of updating for resources integrated in TCRD differs. Text-mined sources are updated more frequently, and changes in the scientific literature allow us to track certain associations sooner. Therefore, selecting one of these sources (as displayed) will show that ACE2 is expressed in the lungs.
Disease details page for Huntington's disease, showing Disease Ontology description and hierarchy (A), and TIN-X plot showing novelty targets and their importance, mapped with a log scale (B).
Ligand details page for acetazolamide, shows ligand description information as well as synonyms and identifiers (A). Target activity is shown with expanded activity for CA2 (B).
Target list described in Target List Search use case (A), and target list described in Binding partner search use case (B). Both panels show selected filters, including the ability to filter target lists by IDG featured sub-lists.
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| Name | Type |
|---|---|
| 3D structures local | drug |
| ACE2 local | gene |
| active ligands local | drug |
| amifampridine local | drug |
| approved drugs local | drug |
| asthma | phenotype |
| biologics local | drug |
| brain tissue | anatomy |
| CAMKK2 | gene |
| Cancer Cell Line Encyclopedia local | cohort |
| ChEMBL local | cohort |
| COVID-19 local | phenotype |
| dark targets local | cohort |
| disease | phenotype |
| Disease of interest local | phenotype |
| DrugCentral local | cohort |
| Gene Ontology local | cohort |
| GTEx | cohort |
| Human Protein Atlas | cohort |
| Human Proteome Map local | cohort |
| Illuminating the Druggable Genome local | cohort |
| IMPC phenotype local | phenotype |
| International Mouse Phenotyping Consortium local | cohort |
| JensenLab PubMed scores local | cohort |
| KCNS2 local | gene |
| Library of Integrated Network-Based Cellular Signatures local | cohort |
| ligand local | drug |
| Ligand local | drug |
| Ligands | drug |
| mouse protein local | gene |
| nervous system phenotype local | phenotype |
| NGL Viewer local | drug |
| nucleus local | anatomy |
| PDB identifiers local | drug |
| Pharos local | cohort |
| Pharos 3.0 local | cohort |
| Rat Genome Database local | cohort |
| rat protein local | gene |
| RGD phenotype local | phenotype |
| SARS-CoV local | drug |
| SARS-CoV-2 local | drug |
| small molecules | drug |
| target local | gene |
| Target local | gene |
| Target Central Resource Database local | cohort |
| targets local | drug |
| Tbio local | cohort |
| Tchem local | cohort |
| Tclin local | cohort |
| TCRD local | cohort |
| Tdark local | cohort |
| tissue | anatomy |
| UniProt | cohort |
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